Inflammatory reactions can provide an essential defense to infection and injury. At the same time, many human diseases or treatments are aggravated by excessive inflammatory reactions brought on by immune responses (e.g., immune responses to organ transplantation). Presently, development of specific and efficacious anti-inflammatory treatment modalities is challenging. For example, use of pharmacologic anti-inflammatory agents (e.g., corticosteroids, NSAIDs, and cytokine antagonists) or immunosuppressive agents (e.g., cyclosporin A, FK 506 and rapamycin) is frequently complicated by adverse events limiting their clinical utility. Therefore, identification of biocompatible agents that reduce immune responses, and preferably inflammation, has important therapeutic implications.
Ningalins comprise a family of 3,4-dihydroxyphenylalanine (DOPA)-derived o-catechol metabolites that include the tunichromes (Bruening, R. C.; et al. J. Am. Chem. Soc. 1985, 107, 5289; Bruening, R. C.; et al. J. Nat. Prod. 1986, 49, 193; Bayer, E; et al. Angew. Chem. Int. Ed. Engl. 1992, 31, 52; Oltz, E. M.; et al. J. Am. Chem. Soc. 1988, 110, 6162; Ryan, D. E.; et al. J. Am. Chem. Soc. 1992, 114, 9659; Taylor, S. W.; et al. Arch. Biochem. Biophys. 1995, 324, 228). Ningalins are believed to be potent reversing agents of multidrug resistance. Ningalins were not heretofore known to be viable therapeutic candidates for reducing inflammation or mediating immunosuppression.